A cohort of anti-human immunodeficiency virus (HIV) positive donors and controls has been under prospective follow-up since 1985 (N Engl J Med 321:917, 1989). At enrollment, 182 subjects were Western blot (WB) positive, including 158 asymptomatic donors, 15 blood recipients, and 9 sexual partners. A control population included 70 anti-HIV reactive donors who were WB negative and 21 who were WB indeterminate. Of the 182 WB-positive subjects, 87 percent were donors, 5 percent sexual partners, and 8 percent blood recipients. Of the 182 WB positives, 46 (25%) are alive and in active followup; 73(40%)are dead, of whom 62(85%)died of AIDS; 63(35%)are lost to follow-up(LTFU);13 of the 73 LTFU were known to have AIDS at the time they left the study. Of the 46 in active followup, 77% are males and 91% were detected at blood donation. Of the 46 active patients, 17 (37%) have had an AIDS defining event. Others have CD4 counts under 300, but have had a stable course even before treatment. A subset of 13 patients have exceeded 10 years of followup and have CD4 counts persistently more than 400 with no AIDS-defining infections and no physical abnormalities except minor adenopathy. Our goal will be to focus on this group in terms of predictive factors for long-term non-progression. We are in the process of measuring serial viral loads in the entire cohort dating back to 1985 and will compare these to CD4 counts and outcome. HIV coreceptors will be measured as indicated. No evidence of HIV infection evolved in the initial anti-HIV positive, but WB-indeterminate or WB-negative subjects. Treatment with HAART therapy is being conducted by personal physicians or through other NIH protocols.